Lymphocyte changes in pregnancy: a comparison of the human immunodeficiency virus infected and non-infected women.

The aim of this study was to assess cellular immunological changes in HIV infected and non-infected normal pregnancies. This was a cross-sectional study of women in the three trimesters of pregnancy and the postpartum period. All participants were asymptomatic. This study showed that absolute numbers of CD4 counts in the HIV infected group were significantly lower than that in the non-infected group, for all periods of gestation studied. The CD8 counts were found to increase postdelivery and may have clinical significance in relation to mother to child transmission. This needs further study with a larger sample size and a longitudinal design method of study.     

Construction and application of a microprojectile system for the transfection of organotypic brain slices

In this study we outline a method for constructing an inexpensive chamber used in the transfection of organotypic brain slices. This chamber differs from most commercially available chambers in that DNA-coated gold microcarriers are directly carried by a flow of helium at low pressure (26 psi). Most other chambers employ macrocarriers onto which DNA-coated gold is first loaded, and then released by a shock of helium onto the reverse side of the macrocarriers. This home constructed device has been successfully employed in the transfection of organotypic brain slices cultured using the air-medium interface method. Mammalian expression vectors containing cytomegalovirus (CMV) and simian virus (SV40) enhancers/promoters were used to express enhanced green fluorescence protein (EGFP). DNA was coated onto 0.6-microm gold microcarriers. Transfected cells were visualised under a fluorescence microscope and included identifiable neurones and oligodendrocytes. Also included in this study are step-by-step methods for the preparation of gold microcarriers and organotypic brain slices.     

Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer.

PURPOSE: The objective of this study was to determine whether the addition of trastuzumab to chemotherapy in the neoadjuvant setting could increase pathologic complete response (pCR) rate in patients with human epidermal growth factor receptor 2 (HER2) -positive disease. PATIENTS AND METHODS: Forty-two patients with HER2-positive disease with operable breast cancer were randomly assigned to either four cycles of paclitaxel followed by four cycles of fluorouracil, epirubicin, and cyclophosphamide or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks. The primary objective was to demonstrate a 20% improvement in pCR (assumed 21% to 41%) with the addition of trastuzumab to chemotherapy. The planned sample size was 164 patients. RESULTS: Prognostic factors were similar in the two groups. After 34 patients had completed therapy, the trial's Data Monitoring Committee stopped the trial because of superiority of trastuzumab plus chemotherapy. pCR rates were 25% and 66.7% for chemotherapy (n = 16) and trastuzumab plus chemotherapy (n = 18), respectively (P = .02). The decision was based on the calculation that, if study continued to 164 patients, there was a 95% probability that trastuzumab plus chemotherapy would be superior. Of the 42 randomized patients, 26% in the chemotherapy arm achieved pCR compared with 65.2% in the trastuzumab plus chemotherapy arm (P = .016). The safety of this approach is not established, although no clinical congestive heart failure was observed. A more than 10% decrease in the cardiac ejection fraction was observed in five and seven patients in the chemotherapy and trastuzumab plus chemotherapy arms, respectively. CONCLUSION: Despite the small sample size, these data indicate that adding trastuzumab to chemotherapy, as used in this trial, significantly increased pCR without clinical congestive heart failure.     

Age has a profound effect on the incidence and significance of chromosome abnormalities in myeloma.

A simple high throughput micro-fluorescence in situ hybridisation technique (FISH) was used to detect chromosome 13 deletions (delta13), immunoglobulin heavy chain (IgH) rearrangements, t(11;14)(q13;q32), t(4;14)(p16;q32), t(14;16)(q23;q32), p53 loss, and numerical changes of chromosomes 3, 6, 7, 9, 10, 11 and 17 in 228 cases of multiple myeloma (MM), including 33 asymptomatic/smouldering MM (SMM). The patients were not part of a clinical trial and were from 30 different hospitals. In all, 98.4% of cases were abnormal, with 43% having IgH rearrangements and 42% Delta13. The low incidence of IgH rearrangements was due to a decrease in this finding with age (P = 0.001) and the relatively high proportion of elderly patients in our study population (41% >70 years old). The incidence of specific IgH translocations was t(4;14) 11%, t(11;14) 16% and t(14;16) 3%. Univariate statistical testing showed delta13 (P = 0.002), and t(14;16) (P = 0.005) to be associated with shorter survival. This effect was exaggerated for patient's aged 70 years or under but no effect on survival was seen for those over 70 years. In younger patients t(4;14) (P = 0.044) and p53 deletion (P < 0.001) were also significant poor prognostic indicators. Multivariate analysis showed delta13 and t(14;16) to be independent prognostic variables when considered with age and clinical parameters.     

Outcome of patients less than 55 years of age with high-risk acute leukemia who did not have an human leukocyte antigen-identical related donor: a long-term study of 97 consecutive patients.

Between January 1993 and December 2000, an unrelated donor search (UDS) was initiated for 97 consecutive patients [46 acute lymphoblastic leukemia (ALL) and 51 acute myeloid leukemia (AML)]. Leukemia was considered to be of poor prognosis in cases of refractory disease (n=70), unfavourable karyotype (n=22) or miscellaneous (n=5). All patients had previously received various chemotherapies and 9 had undergone an autologous stem cell transplantation (SCT). The median age at UDS initiation was 25 (range 2.7-55) years. The median time to identify a suitable living donor or cord blood (CB) was 60 days. Eventually, 33 patients received unrelated allo-SCT (including 9 CB), 12 auto-SCT, 39 chemotherapy and 13 palliative treatment. At a median of 54 months, 18 patients were alive, including 15 in remission. The 4-year overall survival rates were 32%, 37%, 15% and 0% for allo-SCT, auto-SCT, chemotherapy or palliative treatment, respectively. Patients who received either allo- or auto-SCT had better survival than those who did not (P<0.0001). For ALL, only allo-SCT significantly improved survival (P<0.007). Finally, patients who received allo-SCT died less often of relapse than patients who did not (P<0.0001). Unrelated allo-SCT gives a substantial long-term survival and cure in patients with high-risk acute leukemia. For patients who achieve remission and for whom UDS fails, auto-SCT may prove to be a good approach. For patients who fail to enter into remission, intensive salvage chemotherapy has a very limited effect.     

Fludarabine in combination with alemtuzumab is effective and feasible in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: results of a phase II trial.

PURPOSE: To determine the efficacy and safety of a newly developed concomitant administration of fludarabine and alemtuzumab (FluCam) in patients with relapsed or refractory B-cell chronic lymphocytic leukemia (B-CLL). PATIENTS AND METHODS: A total of 36 patients were treated in this phase II study (median age, 61.47 years; mean number of prior chemotherapies, 2.6; Binet stage C, n = 28). After an initial dose escalation of alemtuzumab over 3 days, alemtuzumab 30 mg and fludarabine 30 mg/m2 were administered on 3 consecutive days. Treatment was repeated after 28 days for up to six cycles. Restaging (following National Cancer Institute criteria) was carried out after cycles 2 and 4 and 1 month after the end of treatment. RESULTS: The overall response rate was 83% (11 complete responses, 19 partial responses, one stable disease, and five progressive diseases). Two patients with progressive disease developed fungal pneumonias, and one patient died as a result of Escherichia coli sepsis. Two subclinical cytomegalovirus reactivations occurred. CONCLUSION: The new FluCam regimen is effective and feasible in patients with relapsed and refractory B-CLL.     

Total soluble HLA class I and soluble HLA-G in multiple myeloma and monoclonal gammopathy of undetermined significance.

Serum beta2-microglobulin, the light chain of the HLA class I molecular complex, remains one of the best survival prognostic factors in multiple myeloma, but other HLA class I molecules might be of interest in monoclonal gammopathies. In this study, we evaluate total soluble HLA class I (HLA-Is) and soluble HLA-G (HLA-Gs) in 103 patients with newly diagnosed multiple myeloma, 30 patients with monoclonal gammopathy of undetermined significance (MGUS), and 30 healthy subjects, studying their prognostic value in multiple myeloma. In multiple myeloma patients, HLA-Is and HLA-Gs median values were 0.8 microg/mL and 28 ng/mL, respectively. Median HLA-Is concentration was higher in stage II and III multiple myeloma patients than in stage I multiple myeloma, MGUS, and control patients. Median HLA-Gs was significantly lower in healthy controls than in MGUS and multiple myeloma patients. A high level of HLA-Is (> or =2.1 microg/mL) was predictive of short survival (P = 0.017). For each given level of beta2-microglobulin, the relative risk of death was higher for patients with HLA-Is > or = 2.1 microg/mL than in patients with a lower level (P = 0.047). HLA-Gs, a marker of monoclonal gammopathy, was of no prognostic value, but the addition of HLA-Is to beta2-microglobulin produced an efficient prognostic score (P < 0.0001). HLA-Is is a new marker of multiple myeloma tumor load and provides additional survival prognostic information to beta2-microglobulin.     

Are Essential Medicines in Malaysia Accessible, Affordable and Available?

Objective: To assess the pharmaceutical sector to know whether people have access to essential medicines. Setting: The study was conducted in 20 public health clinics, five public district drug stores and 20 private retail pharmacies selected randomly in five different areas randomly selected (four states and a federal territory). Method: The methodology used was adopted from the World Health Organization study protocol. The degree of attainment of the strategic pharmaceutical objectives of improved access is measured by a list of tested indicators. Access is measured in terms of the availability and affordability of essential medicines, especially to the poor and in the public sector. The first survey in the public health clinics and public district drug stores gathered information about current availability of essential medicines, prevalence of stock-outs and affordability of treatment (except drug stores). The second survey assessed affordability of treatment in public health clinics and private retail pharmacies. Main Outcome Measure Availability, stock-out duration, percent of medicines dispensed, accessibility and affordability of key medicines. Results The average availability of key medicines in the public health clinics for the country was 95.4%. The average stock-out duration of key medicines was 6.5 days. However, average availability of key medicines in the public district drug stores was 89.2%; with an average stock-out duration of 32.4 days. Medicines prescribed were 100% dispensed to the patients. Average affordability for public health clinics was 1.5 weeks salary and for the private pharmacies, 3.7 weeks salary. Conclusions: The present pharmaceutical situation in the context of essential medicines list implementation reflected that the majority of the population in Malaysia had access to affordable essential medicines. If medicines need to be obtained from the private sector, they are hardly affordable. Although the average availability of essential medicines in Malaysia was high being more than 95.0%, in certain areas in Sabah availability was less than 80.0% and still a problem.     

Label-free metabolic imaging of non-alcoholic-fatty-liver-disease (NAFLD) liver by volumetric dynamic optical coherence tomography

Label-free metabolic imaging of non-alcoholic fatty liver disease (NAFLD) mouse liver is demonstrated ex vivo by dynamic optical coherence tomography (OCT). The NAFLD mouse is a methionine choline-deficient (MCD)-diet model, and two mice fed the MCD diet for 1 and 2 weeks are involved in addition to a normal-diet mouse. The dynamic OCT is based on repeating raster scan and logarithmic intensity variance (LIV) analysis that enables volumetric metabolic imaging with a standard-speed (50,000 A-lines/s) OCT system. Metabolic domains associated with lipid droplet accumulation and inflammation are clearly visualized three-dimensionally. Particularly, the normal-diet liver exhibits highly metabolic vessel-like structures of peri-vascular hepatic zones. The 1-week MCD-diet liver shows ring-shaped highly metabolic structures formed with lipid droplets. The 2-week MCD-diet liver exhibits fragmented vessel-like structures associated with inflammation. These results imply that volumetric LIV imaging is useful for visualizing and assessing NAFLD abnormalities.     

Long-Term Effect of Gluten-Free Diets on Nutritional Status,Body Composition,and Associated Factors in Adult Saudi Females with Celiac Disease

This cross-sectional study examines the influence of long-term gluten-free diet (GFD) consumption on nutritional status, body composition, and associated factors in adult Saudi females with celiac diseases (CD). Fifty-one patients who have been diagnosed with CD and have been on GFD for more than 1 year were included in this study where data regarding their dietary pattern, as well as a complete analysis of their anthropometric parameters, vitamins B12 and D levels, and complete blood count (CBC), were collected. Data have shown that all included patients showed a reduced intake in all micro and macro-nutrients, as well as vitamin D, folate, calcium, and iron. However, the vast majority of all measured hematological parameters and blood indices were within the expected reference range. In addition, 51%, 43.1%, and 60.8% of the patients showed low waist/hip ratio (WHR), decreased level of total body fat (BF), and decreased level of visceral fat (VF), respectively, whereas 33.3% were slim. The poor educational level and some psychosocial factors were associated with the poor nutritional status of the patients. In conclusion, the GFD-dependent intake by female patients with CD adversely affects their nutritional intake and anthropometric indices and leads to a deficiency in major nutrients, vitamins, and ions.